There are a variety of sensors within the art for diagnostic testing of materials related to human health, veterinary medical, environmental, biohazard, bioterrorism, agricultural commodity and food safety. The means for diagnostic testing and analysis of chemical and/or biological materials at the point of need remains limited. Diagnostic testing traditionally requires long response times to obtain meaningful data, involves expensive remote or cumbersome laboratory equipment that costs thousands of dollars located in a centralized laboratory, requires large sample sizes, utilizes multiple reagents, demands highly trained users, may require numerous steps, and/or involves significant direct and indirect costs. For instance, in both the veterinary and human diagnostic markets, most tests require that a specimen be collected from the patient and sent to the laboratory, but the results are not available for several hours or days later. As a result, the patient may leave the caregiver's office without confirmation of the diagnosis and the opportunity to begin immediate treatment.
Other problems related to portable devices include diagnostic results that are limited in sensitivity and reproducibility compared to in-laboratory testing. Fast response times are desirable and often critical to the identification of chemical and/or biological materials, such as in providing timely medical attention or in averting the spread or exposure of public health threats. Direct costs relate to the labor, procedures, and equipment required for each type of analysis. Indirect costs partially accrue from the delay time before actionable information can be obtained, e.g., in medical analyses or in the monitoring of chemical processes. Many experts believe that the simultaneous diagnosis and treatment enabled by an effective point of need diagnostic testing system would yield clinical, economic and social benefits. For instance, clinical benefits include faster turnaround of results, reduced time to treatment, reduced disease severity and improved mortality/morbidity. Economic benefits included reduced length of stay, improved utilization, more efficient care delivery and fewer admissions. Social benefits include improved access to healthcare/therapy, higher patient satisfaction and reduced absenteeism.
Various technologies have been utilized to develop sensors to detect and analyze chemical and/or biological materials, but fail to address issues related to traditional detection and analysis systems. For example, some detection systems determine the presence of substances based on electrochemical reactions. Such electrochemical sensors, however, usually have complex sensor arrangements that require substance-recognizing agents, are expensive, are often difficult to miniaturize due to low current densities resulting from smaller sensor structural shapes, and the rate and efficiency of the electrochemical sensor response time may be undesirable as they are controlled by the chemical reactions. Other detection systems are known from chemical laboratory practice, such as the various types of chromatography and spectral analysis. The laboratory systems, however, often do not meet the demands for ruggedness, stability, transportability, and low maintenance and energy consumption required for diagnostic testing outside the laboratory. Bench-top instruments are also often very expensive and require a centralized laboratory to which samples must be sent for testing.
Resonators based on piezoelectric properties of materials have also been used in detecting very small quantities of materials. Piezoelectric resonators used as sensors in such applications are sometimes called “micro-balances.” A piezoelectric resonator is typically constructed as a thin planar layer of crystalline piezoelectric material sandwiched between two electrode layers. When used as a sensor, the resonator is exposed to the material being detected to allow the material to bind on a surface of the resonator.
A conventional way of detecting the amount of the material bound on the surface of a sensing resonator is to operate the resonator as an oscillator at its resonant frequency, as described, for instance, in U.S. Pat. No. 5,932,953 entitled “Method and System for Detecting Material Using Piezoelectric Resonators,” which is incorporated by reference herein. As the material being detected binds on the resonator surface, the oscillation frequency of the resonator is reduced. The change in the oscillation frequency of the resonator, caused by the binding of the material on the resonator surface, is measured and used to calculate the amount of the material bound on the resonator or the rate at which the material accumulates on the resonator surface.
The sensitivity of a piezoelectric resonator as a material sensor is typically proportional to its resonance frequency. Thus, the sensitivities of material sensors based on the popular quartz crystal resonators are limited by their relatively low oscillating frequencies, which typically range from several MHz to about 100 MHz. The development of thin-film resonator (TFR) technology has produced sensors with significantly improved sensitivities. A thin-film resonator is formed by depositing a thin film of piezoelectric material, such as AlN or ZnO, on a substrate. Due to the small thickness of the piezoelectric layer in a thin-film resonator, which is on the order of several microns (μm), the resonant frequency of the thin-film resonator is on the order of 1 GHz or higher. The high resonant frequencies and the corresponding high sensitivities make thin-film resonators useful for material sensing applications.
A significant disadvantage of the conventional approach is the difficulty in separating the real intended material binding signal from spurious environmental effects. During material detection, a sensing resonator is often exposed to different environmental conditions that also tend to alter the resonance properties of the resonator. It is often difficult to isolate the resonance changes caused by the material detected from the resonance changes caused by various environmental conditions without incorporating large, expensive means for environmental isolation.
What is still needed is a simple sensor and resonance shift detection system that is portable for point of need diagnostic testing of chemical and/or biological materials, which not only is simple to use with little or no training, but provides rapid turn-around of reproducibly consistent results at acceptable sensitivity levels, capable of embodiments that can be scaled for manufacturing level utilization, low cost, and capable of transmitting results anywhere to caregivers and patient information systems.